Blocked. Chemo drugs (green) can not enter a pancreatic tumor (blue). White stroma ( insert ) separates the bloodstream from tumor cells (light brown)
Stefanie Reichelt, Michal Al Jacobetz and Kenneth P. Olive. (Box) Kenneth P. Olive
Nearly 95% of patients with pancreatic cancer die within 5 years of diagnosis and traditional chemotherapy does little to save their lives. Now cancer researchers think they know why - and how they could move the defenses of the tumor. The work "has enormous consequences for our approach to treating this disease," says Margaret Tempero, an oncologist at the University of California, San Francisco.
Cancers almost always grow in the system ducts of the pancreas, a spongy fabric handle nestles against the stomach that produces digestive enzymes and hormones such as insulin. Although these tumors are lethal when they spread to other parts of the body, malignant cells are surprisingly rare in the pancreas. biopsies usually turn up a few cancer cells scattered amid masses of stroma, hard layers, fibrous connective tissue that resembles a "big piece of cartilage," says oncologist David Tuveson of Cambridge research Institute in the UK.
This cartilage, Tuveson and colleagues found protects pancreatic tumors of blood treatments carried as chemotherapy. Using genetically engineered to develop pancreatic cancer mice, the team mapped the blood supply of tumors using chemical tracers to mark the bloodstream. They found very little blood vessels and only a third more traffic than in normal tissues. human pancreatic cancer samples told a similar story: lots of fibrous tissue, some blood vessels
If his team could reduce the stroma, Tuveson wondered, could doctors target cancer cells hiding in inside.? The group focused on the signaling pathway hedgehog named capriciously, who helps organize the structure of organisms during embryonic development and promotes the growth of stroma. The researchers treated mice with IPI-926, a drug that inhibits the Hedgehog pathway. Other mice received a standard chemotherapy drug, while yet another group received IPI-926 and the chemotherapy drug.
As the researchers had hoped, IPI-926 dramatically shrank the stroma. And there was a bonus The drug also increased the number of blood vessels into tumors by three to four times. Nourish tumors with additional blood might normally promote cancer growth, but in the case of pancreatic cancer, it was good for drug delivery; Mice given a combination of chemotherapy and IPI-926 has nearly doubled their survival from a median of 11 days to 25 days, the researchers report online today in Science . It is not a cure, Tuveson warns, but the results leaves optimistic. "If we were to double the survival of pancreatic cancer patients who had advanced disease, instead of dying in 6 months, they would be dead in 12 months," he said. Compared to previous medical interventions, "which would be a greater impact than we've ever seen."
Although other factors that can affect blood flow chemotherapy resistance, the study "shows well enough that the cancer cell is not the only thing we need to be worried", they say oncologist James Abbruzzese of the MD Anderson Cancer Center in Houston, Texas. "We really should pay more attention to these cancer-stroma interactions." The next step, he and Tempero say, is whether IPI-926 has any potential as a drug for humans and whether it is safe to use on tumors outside the pancreas.
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